Initial Synthesis of Valoneic and Woodfordinic Acid Dilactones

Wyrepkowski C., Gomes da Costa D., Sinhorin A., Vilegas W., De Grandis R., Resende F., Varanda E., dos Santos L.

Shioe K., Ishikura S., Horino Y., Abe H.

A facile method for the synthesis of dehydrodigallic acid, which is a fundamental structure of ellagitannins, was developed. A classical Ullmann condition was effective for the formation of the highly hindered biaryl ether structure, and we clarified that the suitable protection of the phenolic hydroxy groups was crucial in this reaction. In this way, the synthesis of dehydrodigallic acid and its derivative was successfully performed. The described method would provide a synthetic utility toward ellagitannins.

Boulekbache-Makhlouf L., Meudec E., Mazauric J., Madani K., Cheynier V.

Eucalyptus species are widely cultivated in Mediterranean regions. Moreover, plants of this family have been utilized for medicinal purposes. A number of studies have been devoted to the identification of eucalypt phenolics, all of them have focused on specific families of compounds, and no exhaustive profiling has been reported in leaves of this plant.To develop methods that allows the identification and quantification of different classes of phenolics in Eucalyptus globulus leaf.Acetonic extract was fractionated by chromatography on a Sephadex LH-20 column using consecutive elution with ethanol, methanol and aqueous acetone (60%). High-performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD-ESI/MS) were applied to determine the structure of different compounds. Quantities were evaluated from peak areas in the HPLC profile, using external calibration curves.Fractionation of acetonic extract yielded three fractions: F1, F2 and F3. In total 39 phenolic compounds are detected. Among them: 16 hydrolyzable tannins, 3 terpenyl derivatives, 12 ellagic acid derivatives, 5 flavonols, 2 hydroxybenzoic acids and 1 formylated phloroglucinol. 26 compounds described in this study have not previously detected in leaves of this plant and this is the first report of quercetin 3-O-β-galactoside-6"-O-gallate and cypellogin A and B, in E. globulus plant. Quantitatively, ellagic acid derivatives and sideroxylonal A or B are largely predominant.Fractionation of crude extract by chromatography on Sephadex LH-20 was efficient to separate different molecular weight compounds. HPLC-DAD-ESI/MS enabled detection of gallotannin, ellagitannin and flavonol derivatives, in leaves of E. globulus.

Omar R., Li L., Yuan T., Seeram N.P.

Three new hydrolyzable tannins including two gallotannins, jamutannins A (1) and B (2), and an ellagitannin, iso-oenothein C (3), along with eight known phenolic compounds were isolated from the seeds of Eugenia jambolana fruit. The structures were elucidated on the basis of spectroscopic data analysis. All compounds isolated were evaluated for α-glucosidase inhibitory effects compared to the clinical drug acarbose.

Wu S., Dastmalchi K., Long C., Kennelly E.J.

Many dark-colored fruit juices, rich in anthocyanins, are thought to be important for human health. Joboticaba (Myrciaria cauliflora) fruits, native to Brazil, have phenolics including anthocyanins and are processed into juice and other products. The phenolic constituents in the fruits of jaboticaba were studied by high-performance liquid chromatography coupled with electrospray ionization time-of-flight mass spectrometry. Twenty-two compounds were identified or tentatively determined by detailed analysis of their mass spectral fragmentation patterns; 11 compounds including 7 gallotannins, 2 ellagic acid derivatives, syringin, and its glucoside were detected for the first time in the fruit. The compositional differences among the fruit extracts and their commercial products were also compared by principal component analysis; two anthocyanins, delphinidin 3-O-glucoside and cyanidin-3-O-glucoside, as well as two depsides, jaboticabin and 2-O-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxyphenylacetic acid, present ...

Kiss A.K., Granica S., Stolarczyk M., Melzig M.F.

In the present study, we have investigated the influence of low concentrations of polyphenols (5 μM) on histone acetyltransferase (HAT) and histone deacetylase (HDAC) activity, a monocyte cell system related to the inflammatory process. We selected gallic acid, ellagic acid, oenothein B, valoneic acid dilactone and penta- O -galloyl-β- d -glucose, which are known to affect inflammatory responses, such as IL-6 secretion and/or NF-κB down-regulation and polyphenol metabolites (urolithins A, B and C). TNF-α stimulation resulted in a reduction of THP-1 cell viability by 28.9%, reduced HDAC activity from 25.2 to 13.5 pmol/μg protein and increased HAT activity from 24.0 to 45.5 pmol/μg protein. The coincubation with ellagic acid and oenothein B restored the viability and reversed the effect of TNF-α on HAT and HDAC activities. Urolithins B and C, gallic acid and penta- O -galloyl-β- d -glucose only showed significant reductions of HAT activity, by 40–50%. Our results prove that polyphenols act as epigenetic modulators.

Fischer U.A., Carle R., Kammerer D.R.

Phenolic compounds were extracted from pomegranate (Punica granatum L.) peel, mesocarp and arils. Extracts and juices were characterised by HPLC-DAD-ESI/MS(n). In total, 48 compounds were detected, among which 9 anthocyanins, 2 gallotannins, 22 ellagitannins, 2 gallagyl esters, 4 hydroxybenzoic acids, 7 hydroxycinnamic acids and 1 dihydroflavonol were identified based on their UV spectra and fragmentation patterns in collision-induced dissociation experiments. To the best of our knowledge, cyanidin-pentoside-hexoside, valoneic acid bilactone, brevifolin carboxylic acid, vanillic acid 4-glucoside and dihydrokaempferol-hexoside are reported for the first time in pomegranate fruits. Furthermore, punicalagin and pedunculagin I were isolated by preparative HPLC and used for quantification purposes. The ellagitannins were found to be the predominant phenolics in all samples investigated, among them punicalagin ranging from 11 to 20g per kilogram dry matter of mesocarp and peel as well as 4-565mg/L in the juices. The isolated compounds, extracts and juices were also assessed by the TEAC, FRAP and Folin-Ciocalteu assays revealing high correlation (R(2)=0.9995) of the TEAC and FRAP values, but also with total phenolic contents as determined by the Folin-Ciocalteu assay and by HPLC. Selection of raw materials, i.e. co-extraction of arils and peel, and pressure, respectively, markedly affected the profiles and contents of phenolics in the pomegranate juices, underlining the necessity to optimise these parameters for obtaining products with well-defined functional properties.

Fernandes A., Sousa A., Mateus N., Cabral M., de Freitas V.

The aim of the present work was to identify the extractable phenolic compounds present in cork from Quercus suber L. The structures of thirty three compounds were tentatively identified by liquid chromatography coupled to electrospray ionisation mass spectrometry (HPLC–DAD/ESI–MS). The majority of those compounds were gallic acid derivatives, in the form of either galloyl esters of glucose (gallotannins), combinations of galloyl and hexahydroxydiphenoyl esters of glucose (ellagitannins), dehydrated tergallic-C-glucosides or ellagic acid derivatives. Others were found to correspond to low molecular weight phenolic compounds, like acids and aldehydes. Mongolicain, a flavanoellagitannin in which hydrolysable tannin and flavan-3-ol moieties are connected through a carbon–carbon linkage, was also detected in cork from Q. suber L. The results illustrate the rich array of phenolic compounds present in cork.

Shioe K., Sahara Y., Horino Y., Harayama T., Takeuchi Y., Abe H.

Ellagitannins possess a wide range of biological activities and remarkable structural diversity, which commonly include an axially chiral biaryl unit. This paper describes syntheses of all-methylated versions of isorugosin B and rugosin B, which are regioisomeric, ellagitannin-related compounds. The key features of these syntheses involve the construction of an axially chiral biaryl function on a sugar moiety through a Pd-catalyzed intramolecular biaryl coupling reaction, Bringmann’s atroposelective lactone opening reaction, and a two-step ester formation. This is the first synthetic approach for generating ellagitannins featuring a valoneoyl group.

Quideau S., Deffieux D., Douat-Casassus C., Pouységu L.

Eating five servings of fruits and vegetables per day! This is what is highly recommended and heavily advertised nowadays to the general public to stay fit and healthy! Drinking green tea on a regular basis, eating chocolate from time to time, as well as savoring a couple of glasses of red wine per day have been claimed to increase life expectancy even further! Why? The answer is in fact still under scientific scrutiny, but a particular class of compounds naturally occurring in fruits and vegetables is considered to be crucial for the expression of such human health benefits: the polyphenols! What are these plant products really? What are their physicochemical properties? How do they express their biological activity? Are they really valuable for disease prevention? Can they be used to develop new pharmaceutical drugs? What recent progress has been made toward their preparation by organic synthesis? This Review gives answers from a chemical perspective, summarizes the state of the art, and highlights the most significant advances in the field of polyphenol research.

de la Rosa L.A., Alvarez-Parrilla E., Shahidi F.

The phenolic composition and antioxidant activity of pecan kernels and shells cultivated in three regions of the state of Chihuahua, Mexico, were analyzed. High concentrations of total extractable phenolics, flavonoids, and proanthocyanidins were found in kernels, and 5-20-fold higher concentrations were found in shells. Their concentrations were significantly affected by the growing region. Antioxidant activity was evaluated by ORAC, DPPH•, HO•, and ABTS•-- scavenging (TAC) methods. Antioxidant activity was strongly correlated with the concentrations of phenolic compounds. A strong correlation existed among the results obtained using these four methods. Five individual phenolic compounds were positively identified and quantified in kernels: ellagic, gallic, protocatechuic, and p-hydroxybenzoic acids and catechin. Only ellagic and gallic acids could be identified in shells. Seven phenolic compounds were tentatively identified in kernels by means of MS and UV spectral comparison, namely, protocatechuic aldehyde, (epi)gallocatechin, one gallic acid-glucose conjugate, three ellagic acid derivatives, and valoneic acid dilactone.

Boulekbache-Makhlouf L., Meudec E., Chibane M., Mazauric J., Slimani S., Henry M., Cheynier V., Madani K.

A method based on high-performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD-ESI-MS) following fractionation by chromatography on a Sephadex LH-20 column has been developed to determine the phenolic composition of fruit of Eucalyptus globulus growing in Algeria. The presence of 18 gallotannins, 26 ellagitannins, and 2 flavonols was established. Tentative identification is provided for these compounds on the basis of UV−visible spectra and mass spectrometry data. Most compounds described in this study have not previously detected in fruit of E. globulus. Moreover, this is the first report of methyl digalloyl diglucose, 3,3′-O-dimethylellagic acid 4-O-β-glucopyranoside, ellagic acid hexose, methyl ellagic acid pentose, methyltetragalloylglucose, and valoneic acid isomers (sanguisorbic, flavogallic acid dilactone) in the genus Eucalyptus. Quantitatively, ellagic acid and its derivatives, including ellagitannins, are largely predominant.

Ochir S., Nishizawa M., Park B.J., Ishii K., Kanazawa T., Funaki M., Yamagishi T.

The 50% aqueous ethanol extracts of petals of Rosa gallica collected in Xinjiang province, China, exhibited potent inhibitory effects against α-amylase and α-glucosidase. As the active principles, seven hydrolysable tannins were isolated from this species for the first time and elucidated by NMR and ESI-TOF-MS analysis. Quantitative analysis by ultra-performance liquid chromatography demonstrated that the contents of these hydrolysable tannins were 3–5% of the dry weight of the petals, and the hydrolysable tannins must be related to the medicinal utilization of this species.

Yoshida T., Amakura Y., Yoshimura M.

Fernandes A., Fernandes I., Cruz L., Mateus N., Cabral M., de Freitas V.

Phenolic compounds, namely, hydrolyzable tannins and low molecular weight phenolic compounds, were isolated and purified from Portuguese cork from Quercus suber L. Some of these compounds were studied to evaluate their antioxidant activity, including free-radical scavenging capacity (DPPH method) and reducing capacity (FRAP method). All compounds tested showed significant antioxidant activity, namely, antiradical and reducing properties. The antiradical capacity seemed to increase with the presence of galloyl groups. Regarding the reducing capacity, this structure-activity relationship was not so clear. These compounds were also studied to evaluate the growth inhibitory effect on the estrogen responsive human breast cancer cell line (ER+) MCF-7 and two other colon cancer cell lines (Caco-2 and HT-29). Generally, all the compounds tested exhibited, after a continuous exposure during a 48 h period, a dose-dependent growth inhibitory effect. Relative inhibitory activity was primarily related to the number of phenolic hydroxyl groups (galloyl and HHDP moieties) found in the active structures, with more groups generally conferring increased effects, except for HHDP-di-galloyl-glucose. Mongolicain B showed a greater potential to inhibit the growth of the three cell lines tested, identical to the effect observed with castalagin. Since these compounds are structurally related with each other, this activity might be based within the C-glycosidic ellagitannin moiety.

Yashunsky D.V., Egorov A.M., Nifantiev N.E.

Substituted β-glucosides of gallic acid and resorcinol, occurring naturally in trace amounts, as well as their O-gallates, which are of interest as covalent blockers of the main protease of the SARS-CoV-2 virus, were synthesized.

Ikeuchi K.

Hashimoto H., Ishimoto T., Konishi H., Hirokane T., Wakamori S., Ikeuchi K., Yamada H.

Herein, a practical synthesis of the macaranoyl group contained in ellagitannins, i.e., a C–O digallate structure with a tetra-ortho-substituted diaryl ether bond, is described. The methodology inv...

Abe H., Imai H., Ogura D., Horino Y.

Ikeuchi K., Wakamori S., Hirokane T., Yamada H.

Santos C.M., Silva A.M.

This is a personal overview of the most exciting chemistry on the synthesis of O- and S-6-membered heterocycles published in 2016. Novel approaches for the synthesis of a huge variety of natural compounds, specific reactions, and reagents for the preparation of natural and synthetic pyrans, chromenes and chromans, isochromenes and isochromans, pyranones, coumarins and isocoumarins, chromones and chromanones, xanthenes and xanthones, thiopyrans and analogs, dioxanes, dithiins, and also oxathianes are highlighted.

Abe H.

Yamada H., Hirokane T., Ikeuchi K., Wakamori S.

This account describes methods for synthesizing natural ellagitannins. The ellagitannins, a class of polyphenols, has a wide variety of chemical structures and biological activities. Here, we focus on three topics, which are the synthesis of the hexahydroxydiphenoyl group, construction of the hexahydroxydiphenoyl bridge, and synthesis of C–O digallates. The hexahydroxydiphenoyl group and the C–O digallates are C–C and C–O coupled galloyl groups, respectively, both group of which are the two major components of ellagitannins. By combining methods described in this account, many ellagitannins might be synthesized.